The first paper from a multi-year clinical research study has been published in The Lancet Infectious Diseases: Dynamics of Endemic Virus Re-emergence in Children in the USA Following the COVID-19 Pandemic (2022-2023): A Longitudinal Immunoepidemiologic Surveillance Study and demonstrates how the approach can improve modeling to better predict future outbreaks.
The paper shares findings from a multicenter clinical research study, one of many studies that are part of the recently launched PREMISE (Pandemic Response Repository through Microbial and Immune Surveillance and Epidemiology) program, led by Dr. Daniel Douek at the National Institutes of Health's (NIH) Vaccine Research Center (VRC). Data collected during the first year of the PREMISE study, 2022-2023, shows for the first time how non-pharmaceutical interventions such as masking and distancing targeted towards SARS-CoV-2 during the pandemic also decreased circulation rates of and population immunity to common respiratory pathogens in children. The study provides new evidence-based insight into what was driving the large post-pandemic rebound in these diseases and enables more accurate predictions for the future.
This study is a partnership between PREMISE and clinical research sites at academic institutions led by principal investigator Kevin Messacar, MD, PhD, infectious disease specialist at Children's Hospital Colorado , at the central site at University of Colorado Anschutz Medical Campus and Children's Hospital Colorado with additional study sites at University of North Carolina, Weill Cornell Medicine and the University of Alabama at Birmingham.
The PREMISE study conducted immunologic surveillance on children younger than 10 years old, by enrolling them and following them for over a year. Through repeat blood sampling, the team could determine what children at varying young ages had immunity to and what they were susceptible to. Through respiratory sampling during illness, researchers were able to determine what infections they experienced. The data showed that most younger children lacked immunity to many normal respiratory viruses during the pandemic, suggesting they had not been exposed, as they typically would have, due to prevention measures in place. Following the lifting of pandemic measures, the level of immunity rose across all pathogens studied, reflective of the unprecedented widespread resurgence of these viruses in children after the end of the pandemic.
While most research studies target a specific disease, samples from PREMISE were tested for many common and emerging respiratory viruses, including RSV, influenza and enterovirus D68 (EV-D68), which can cause the polio-like illness, acute flaccid myelitis. The data allowed experts to recreate past circulation patterns and model predictions for future outbreaks with greater accuracy and precision. They showed that PREMISE data from 2022-23 could be used to accurately predict the subsequent wave of disease of the emerging pathogen EV-D68 that occurred in 2024.
"Four cohorts of almost 1,000 children have provided an invaluable bank of samples and data," said lead author Hai Nguyen-Tran, MD, infectious disease specialist at Children's Hospital Colorado and assistant professor at University of Colorado School of Medicine. "These are being used to develop 'on the shelf' medical countermeasures, such as antibody treatments and vaccines, for pathogens of interest. Instead of starting from scratch, this study gives us a head start to understand, predict and prepare for future pandemics."
Samples and data from the PREMISE study will also be used to learn which parts of viruses the human immune system attacks to become immune, so teams can better design new antibody treatments and effective vaccines to mimic this response.
"In the future, this type of immune surveillance can be used to better understand the impact of public interventions on population immunity and future waves of disease," said Dr. Messacar, who is also a professor at University of Colorado School of Medicine. "PREMISE is a great example of a successful research partnership between NIH scientists and clinical researchers in academia, leading to concrete deliverables such as vaccine candidates and monoclonal antibodies that can directly impact public health."
This study is fully funded by a subcontract with Frederick National Laboratory for Cancer Research (FNLCR), currently operated by Leidos Biomedical Research, Inc. through Agreement 21X192QT1. FNLCR funding was provided by the NIH Vaccine Research Center within NIAID. The total project funding is $7.98 million over five years. No financing for this project was supplied by nongovernmental sources.
